The process of new drug development necessarily involves conducting a clinical trial (“human clinical trial”), which involves administration into the human body and verification of the effect, under the regulation of the Act on Pharmaceuticals and Medical Devices and such human clinical trials and animal testing entail enormous development costs. The cost of overall new drug development has recently increased with these development costs being the greatest cause. A major cause of the cost is that insufficient efficacy and toxicity of some drug candidates are not detected in non-clinical animal experiments in the earlier period of the development process and the insufficient efficacy or the toxicity may be found for the first time in a human clinical trial in the later period of the development process, failing to avoid useless development costs and costs for the human clinical trial.
In this context, it is important to select new drug candidate that have the efficacy and no toxicity early in order to increase the clinical success rate and reduce the new drug development cost. Therefore, many pharmaceutical companies desire in vitro evaluation systems allowing good predictions of pharmacokinetics of administered drugs in the human body using human cells in an early stage of drug development, instead of narrowing down drug candidates solely depending on animal experiments, which have poor correlations with properties of human cells. However, no techniques have been established to attain and analyze total pictures of pharmacokinetics, including uptake, metabolism, excretion through bile ducts and blood vessels, of administered candidate pharmaceutical compounds using cells.
A drug needs to be taken up by the liver and metabolized there into a metabolite or left as an original compound (a parent compound) without being metabolized, then excreted to the basolateral side, and recirculated in the bloodstream to the target organ in order to exhibit its efficacy in the body. Therefore, such an in vitro testing system that can measure the amount of a recirculating candidate pharmaceutical compound excreted to the basolateral side after administration and evaluate the efficacy, which is one of the most important indexes in the new drug development, could be a very useful pharmacokinetics evaluating system. In addition, such a testing system would provide a total picture of the pharmacokinetics including the amount excreted from cells into bile duct (the amount of loss), which is the amount excreted into a bile duct and then out of the body as urine or feces, and the amount retained in the cells and thereby the distribution ratio of such fractions.
Patent Literature 1 and 2 disclose techniques for administering a drug to culture cells and evaluating the amount excreted from bile ducts of the cells (the amount of loss). These evaluation methods evaluate the amount of drug loss, which is an amount of a drug that is administered, but excreted into a bile duct without exhibiting toxicity or efficacy and then excreted out of the body as urine or feces.